ACTH and glucocorticoids have a dramatic effect in the control of a devastating type of epilepsy in young children - infantile myoclonic seizures. They may also be useful in demyelinating and other diseases of the nervous system. This is a study of the biochemical basis for this action using the developing mouse brain in vivo as the target organ and hydrocortisone as the selected hormone. Preliminary work in our laboratory showed that hydrocortisone treatment of immature mice increased brain glucose, ATP, P-creatine and glycogen levels. Hepatic glycogen and plasma beta-hydroxybutyrate concentrations were also elevated. In addition, hydrocortisone stimulated glycerol phosphate dehydrogenase (glycerol-1-P DH) enzyme activity in brain. The increased energy reserve in brain, glycogen stores in liver and supply of ketones from the blood as metabolic fuels for cerebral ATP production in the brains of hydrocortisone-treated animals suggested possible mechanisms for its clinical usefulness in neurological disorders. Increased glycerol phosphate dehydrogenase has a function in lipid formation (and myelination) in developing brain. Based on the preliminary findings, the proposed research concerns the effects of hydrocortisone on ketogenesis, brain ketone body transport, cerebral glucose utilization, and on enzymes of ketone body utilization in brain. The time course of the observed glycerol phosphate dehydrogenase induction will be determined in regions of brain. Steroid effects on the brain (Na ion plus K ion)-activated ATP hydrolyzing enzyme system (Na ion minus K ion ATPase) will also be examined. Hydrocortisone is a known inducer of this enzyme in developing mammalian brain; this effect offers a possible explanation for the benficial action of ACTH and glucocorticoids in infantile seizures.